Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy.

Abstract

In this study, we report the previously unknown mechanism of inducing robust anti-melanoma immunity by the vitiligo-inducing compound monobenzone. We show monobenzone to increase melanocyte and melanoma cell immunogenicity by forming quinone-haptens to the tyrosinase protein and by inducing the release of tyrosinase- and melanoma antigen recognized by T cells-1 (MART-1)-containing CD63+ exosomes following melanosome oxidative stress induction. Monobenzone further augments the processing and shedding of melanocyte-differentiation antigens by inducing melanosome autophagy and enhanced tyrosinase ubiquitination, ultimately activating dendritic cells, which induced cytotoxic human melanoma-reactive T cells. These T cells effectively eradicate melanoma in vivo, as we have reported previously. Monobenzone thereby represents a promising and readily applicable compound for immunotherapy in melanoma patients.

• Authors: Jasper G van den Boorn, Daisy I Picavet, Paul F van Swieten, Henk A van Veen, Debby Konijnenberg, Peter A van Veelen, Toni van Capel, Esther C de Jong, Eric A Reits, Jan W Drijfhout, Jan D Bos, Cornelis J M Melief, Rosalie M Luiten
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 6 Pg. 1240-51 (Jun 2011) ISSN: 1523-1747 [Electronic] United States
• PMID: 21326294 (Publication Type: Journal Article)

Chemical References

• HLA-DR Antigens
• Haptens
• Hydroquinones
• Melanins
• Reactive Oxygen Species
• monobenzone
• Monophenol Monooxygenase

Topics

• Autoimmunity (drug effects)
• Autophagy (drug effects)
• Dendritic Cells (immunology)
• HLA-DR Antigens (analysis)
• Haptens (metabolism)
• Humans
• Hydroquinones (pharmacology)
• Lysosomes (metabolism)
• Melanins (biosynthesis)
• Melanocytes (drug effects, immunology)
• Melanoma (immunology, therapy)
• Melanosomes (drug effects, physiology)
• Monophenol Monooxygenase (immunology, metabolism)
• Reactive Oxygen Species (metabolism)
• Skin Pigmentation (drug effects)
• T-Lymphocytes (drug effects, immunology)
• Ubiquitination